ArticleCancer research2009
Acquired resistance to 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) in glioblastoma cells.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 60 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
60 citing papers in PubMed, 124 citations in OpenAlex.
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- Combination Strategies with HSP90 Inhibitors in Cancer Therapy: Mechanisms, Challenges, and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Insight into the structural and dynamic properties of novel HSP90 inhibitors through DFT calculations and molecular dynamics simulations.Journal of molecular modeling · 2024Article
- Impact of NQO1 dysregulation in CNS disorders.Journal of translational medicine · 2024Review
- Pan-cancer analysis of SERPINE family genes as biomarkers of cancer prognosis and response to therapy.Frontiers in molecular biosciences · 2023Article
- Targeting HSP90 as a Novel Therapy for Cancer: Mechanistic Insights and Translational Relevance.Cells · 2022Review
- Novel Drugs with High Efficacy against Tumor Angiogenesis.International journal of molecular sciences · 2022Review
- Positive regulation of ataxia-telangiectasia-mutated protein (ATM) by E2F transcription Factor 1 (E2F-1) in cisplatin-resistant nasopharyngeal carcinoma cells.World journal of surgical oncology · 2022Article
- Preferential radiosensitization to glioblastoma cancer stem cell-like cells by a Hsp90 inhibitor, N-vinylpyrrolidone-AUY922.Oncology letters · 2022Article
- Robust metabolic transcriptional components in 34,494 patient-derived cancer-related samples and cell lines.Cancer & metabolism · 2021Article
- Predicting tumor response to drugs based on gene-expression biomarkers of sensitivity learned from cancer cell lines.BMC genomics · 2021Article
- HSP90 inhibitor 17AAG attenuates sevoflurane-induced neurotoxicity in rats and human neuroglioma cells via induction of HSP70.Journal of translational medicine · 2020Article
- Inhibitors of HSP90 in melanoma.Apoptosis : an international journal on programmed cell death · 2020Review
- Heat Shock Proteins in Glioblastoma Biology: Where Do We Stand?International journal of molecular sciences · 2019Review
- 17-Aminogeldanamycin selectively diminishes IRE1α-XBP1s pathway activity and cooperatively induces apoptosis with MEK1/2 and BRAFApoptosis : an international journal on programmed cell death · 2019Article
- Overcoming acquired resistance to HSP90 inhibition by targeting JAK-STAT signalling in triple-negative breast cancer.BMC cancer · 2019Article
- Therapies targeting the signal pathways of pheochromocytoma and paraganglioma.OncoTargets and therapy · 2019Article
- The germline genetic component of drug sensitivity in cancer cell lines.Nature communications · 2018Article
- Pharmacological targeting of HSP90 with 17-AAG induces apoptosis of myogenic cells through activation of the intrinsic pathway.Molecular and cellular biochemistry · 2018Article
- Cdc7-Dbf4-mediated phosphorylation of HSP90-S164 stabilizes HSP90-HCLK2-MRN complex to enhance ATR/ATM signaling that overcomes replication stress in cancer.Scientific reports · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Heat shock protein 90 (HSP90) inhibitors, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin), which is currently in phase II/phase III clinical trials, are promising new anticancer agents. Here, we explored acquired resistance to HSP90 inhibitors in glioblastoma (GB), a primary brain tumor with poor prognosis. GB cells were exposed continuously to increased 17-AAG concentrations. Four 17-AAG-resistant GB cell lines were generated. High-resistance levels with resistance indices (RI = resistant line IC(50)/parental line IC(50)) of 20 to 137 were obtained rapidly (2-8 weeks). After cessation of 17-AAG exposure, RI decreased and then stabilized. Cross-resistance was found with other ansamycin benzoquinones but not with the structurally unrelated HSP90 inhibitors, radicicol, the purine BIIB021, and the resorcinylic pyrazole/isoxazole amide compounds VER-49009, VER-50589, and NVP-AUY922. An inverse correlation between NAD(P)H/quinone oxidoreductase 1 (NQO1) expression/activity and 17-AAG IC(50) was observed in the resistant lines. The NQO1 inhibitor ES936 abrogated the differential effects of 17-AAG sensitivity between the parental and resistant lines. NQO1 mRNA levels and NQO1 DNA polymorphism analysis indicated different underlying mechanisms: reduced expression and selection of the inactive NQO1*2 polymorphism. Decreased NQO1 expression was also observed in a melanoma line with acquired resistance to 17-AAG. No resistance was generated with VER-50589 and NVP-AUY922. In conclusion, low NQO1 activity is a likely mechanism of acquired resistance to 17-AAG in GB, melanoma, and, possibly, other tumor types. Such resistance can be overcome with novel HSP90 inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.